Source: European Medicines Agency (EU) Revision Year: 2025 Publisher: Bristol-Myers Squibb Pharma EEIG, Plaza 254, Blanchardstown Corporate Park 2, Dublin 15, D15 T867, Ireland
Reblozyl is indicated in adults for the treatment of transfusion-dependent anaemia due to very low, low and intermediate-risk myelodysplastic syndromes (MDS) (see section 5.1).
Reblozyl is indicated in adults for the treatment of anaemia associated with transfusion-dependent and non-transfusion-dependent beta-thalassaemia (see section 5.1).
Treatment should be initiated by a physician experienced in treatment of haematological diseases.
Prior to each Reblozyl administration, the haemoglobin (Hb) level of patients should be assessed. In case of a red blood cell (RBC) transfusion occurring prior to dosing, the pre-transfusion Hb level must be considered for dosing purposes.
The recommended starting dose of Reblozyl is 1 mg/kg administered once every 3 weeks.
The recommended desired Hb concentration range is between 10 g/dL and 12 g/dL. Dose increase for insufficient response is provided below.
Table 1. Dose increase for insufficient response:
| Dose at 1 mg/kg | Dose increase |
| If after at least 2 consecutive doses at 1 mg/kg, a patient: • is not RBC transfusion-free, or • does not reach Hb concentration of ≥ 10 g/dL and the Hb increase is < 1 g/dL | • Dose should be increased to 1.33 mg/kg |
| Dose at 1.33 mg/kg | Dose increase |
| If after at least 2 consecutive doses at 1.33 mg/kg, a patient: • is not RBC transfusion-free, or • does not reach Hb concentration of ≥ 10 g/dL and the Hb increase is < 1 g/dL | • Dose should be increased to 1.75 mg/kg |
The dose increase should not occur more frequently than every 6 weeks (2 administrations) and should not exceed the maximum dose of 1.75 mg/kg every 3 weeks. The dose should not be increased immediately after a dose delay.
For patients with a pre-dose Hb level of > 9 g/dL and who have not yet achieved transfusion independence, a dose increase may be required at the physician’s discretion; the risk of Hb increasing above the target threshold with concomitant transfusion cannot be excluded.
If a patient loses response (i.e. transfusion independence), the dose should be increased by one dose level (see Table 2).
In patients who do not achieve a response, defined as a reduction in RBC transfusion burden of at least a third after ≥ 2 consecutive doses (6 weeks), at the 1 mg/kg starting dose, the dose should be increased to 1.25 mg/kg. The dose should not be increased beyond the maximum dose of 1.25 mg/kg every 3 weeks.
If a patient loses response (if the RBC transfusion burden increases again after an initial response) the dose should be increased by one dose level (see Table 3).
In patients who do not achieve or maintain a response, defined as an increase from baseline in pre-dose Hb of ≥ 1 g/dL, after ≥ 2 consecutive doses (6 weeks) at the same dose level (in absence of transfusions, i.e. at least 3 weeks after the last transfusion), the dose should be increased by one dose level (see Table 3). The dose should not exceed the maximum dose of 1.25 mg/kg every 3 weeks.
Increase to next dose level based on current dose is provided below.
Table 2. Increase to next dose level for MDS:
| Current dose | Increased dose |
| 0.8 mg/kg | 1 mg/kg |
| 1 mg/kg | 1.33 mg/kg |
| 1.33 mg/kg | 1.75 mg/kg |
Table 3. Increase to next dose level for β-thalassaemia:
| Current dose | Increased dose |
| 0.6 mg/kg* | 0.8 mg/kg |
| 0.8 mg/kg | 1 mg/kg |
| 1 mg/kg | 1.25 mg/kg |
* Applicable only to non-transfusion-dependent β-thalassaemia.
In case of Hb increase > 2 g/dL within 3 weeks in absence of transfusion compared with the Hb value at previous dose, Reblozyl dose should be reduced by one dose level.
If the Hb is ≥ 12 g/dL in the absence of transfusion for at least 3 weeks, the dose should be delayed until the Hb is ≤ 11 g/dL. If there is also a concomitant rapid increase in Hb from the Hb value at previous dose (> 2 g/dL within 3 weeks in absence of transfusion), a dose reduction to one step down should be considered after the dose delay.
Dose should not be reduced below 0.8 mg/kg (for MDS or transfusion-dependent β-thalassaemia) and below 0.6 mg/kg (for non-transfusion-dependent β-thalassaemia).
Reduced dose during treatment with luspatercept are provided below.
Table 4. Reduced dose for MDS:
| Current dose | Reduced dose |
| 1.75 mg/kg | 1.33 mg/kg |
| 1.33 mg/kg | 1 mg/kg |
| 1 mg/kg | 0.8 mg/kg |
Table 5. Reduced dose for β-thalassaemia:
| Current dose | Reduced dose |
| 1.25 mg/kg | 1 mg/kg |
| 1 mg/kg | 0.8 mg/kg |
| 0.8 mg/kg | 0.6 mg/kg* |
* Applicable only to non-transfusion-dependent β-thalassaemia.
Instructions on dose interruptions or reductions for luspatercept treatment-related adverse reactions are outlined in Table 6.
Table 6. Dose modification instructions:
| Treatment-related adverse reactions* | Dose instructions |
| Grade 2 adverse reactions (see section 4.8), including Grade 2 hypertension (see sections 4.4 and 4.8) | • Interrupt treatment • Restart at previous dose when adverse reaction has improved or returned to baseline |
| Grade ≥ 3 hypertension (see sections 4.4 and 4.8) | • Interrupt treatment • Restart at reduced dose once the blood pressure is controlled as per dose reduction guidance |
| Other persistent Grade ≥ 3 adverse reactions (see section 4.8) | • Interrupt treatment • Restart at previous dose or at reduced dose when adverse reaction has improved or returned to baseline as per dose reduction guidance |
| Extramedullary haemopoiesis (EMH) masses causing serious complications (see sections 4.4 and 4.8) | • Discontinue treatment |
* Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: life-threatening.
In case of a missed or delayed scheduled treatment administration, the patient should be administered Reblozyl as soon as possible and dosing continued as prescribed with at least 3 weeks between doses.
If patients experience a loss of response to Reblozyl, causative factors (e.g. a bleeding event) should be assessed. If typical causes for a loss of haematological response are excluded, dose increase should be considered as described above for the respective indication being treated (see Table 2 and Table 3).
Reblozyl should be discontinued if patients do not experience a reduction in transfusion burden (for transfusion-dependent β-thalassaemia patients), or an increase from baseline Hb in the absence of transfusions (for non-transfusion-dependent β-thalassaemia patients), or a decrease in transfusion burden including no increase from baseline Hb (for MDS patients) after 9 weeks of treatment (3 doses) at the maximum dose level, if no alternative explanations for response failure are found (e.g. bleeding, surgery, other concomitant illnesses) or if unacceptable toxicity occurs at any time.
No starting dose adjustment is required for Reblozyl (see section 5.2). Limited data are available in β-thalassaemia patients ≥ 60 years of age.
No starting dose adjustment is required for patients with total bilirubin (BIL) > upper limit of normal (ULN) and/or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 3 x ULN (see section 5.2).
No specific dose recommendation can be made for patients with ALT or AST ≥ 3 x ULN or liver injury CTCAE Grade ≥ 3 due to lack of data (see section 5.2).
No starting dose adjustment is required for patients with mild or moderate renal impairment (individual estimated glomerular filtration rate [eGFR] 30 to 89 mL/min).
No specific dose recommendation can be made for patients with severe renal impairment (individual eGFR < 30 mL/min) due to lack of clinical data (see section 5.2). Patients with renal impairment at baseline have been observed to have higher exposure (see section 5.2). Consequently, these patients should be closely monitored for adverse reactions and dose adjustment should be managed accordingly (see Table 6).
There is no relevant use of Reblozyl in the paediatric population for the indication of myelodysplastic syndromes, or in paediatric patients less than 6 years of age in β-thalassaemia. The safety and efficacy of Reblozyl in the paediatric patients aged from 6 years to less than 18 years have not yet been established in β-thalassaemia. For non-clinical data, see section 5.3.
For subcutaneous use.
After reconstitution, Reblozyl solution should be injected subcutaneously into the upper arm, thigh or abdomen. The exact total dosing volume of the reconstituted solution required for the patient should be calculated and slowly withdrawn from the single-dose vial(s) into a syringe.
The recommended maximum volume of medicinal product per injection site is 1.2 mL. If more than 1.2 mL is required, the total volume should be divided into separate similar volume injections and administered across separate sites using the same anatomical location but on opposite sides of the body.
If multiple injections are required, a new syringe and needle must be used for each subcutaneous injection. No more than one dose from a vial should be administered.
If the Reblozyl solution has been refrigerated after reconstitution, it should be removed from the refrigerator 15-30 minutes prior to injection to allow it to reach room temperature. This will allow for a more comfortable injection.
For instructions on reconstitution of the medicinal product before administration, see section 6.6.
Overdose with luspatercept may cause an increase of Hb values above the desired level. In the event of an overdose, treatment with luspatercept should be delayed until Hb is ≤ 11 g/dL.
Unopened vial:
5 years.
After reconstitution:
When stored in the original container, chemical and physical in-use stability of the reconstituted medicinal product has been demonstrated for up to 8 hours at room temperature (≤25°C) or for up to 24 hours at 2°C-8°C.
From a microbiological point of view, the medicinal product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and should not be longer than 24 hours at 2°C-8°C.
Do not freeze the reconstituted solution.
Store in a refrigerator (2°C-8°C).
Do not freeze.
Store in the original carton in order to protect from light.
For storage conditions after reconstitution of the medicinal product, see section 6.3.
Reblozyl 25 mg powder for solution for injection: 3 mL Type I glass vial with a hydrophobic inner coating closed with a bromobutyl rubber stopper and aluminium seal with yellow polypropylene flip-off cap.
Reblozyl 75 mg powder for solution for injection: 3 mL Type I glass vial with a hydrophobic inner coating closed with a bromobutyl rubber stopper and aluminium seal with orange polypropylene flip-off cap.
Pack size: 1 vial.
Reblozyl must be reconstituted gently prior to administration. Aggressive shaking should be avoided.
Reblozyl is supplied as a lyophilised powder for reconstitution before use. Only water for injections (WFI) should be used when reconstituting Reblozyl.
The appropriate number of Reblozyl vials should be reconstituted to achieve the desired dose. A syringe with appropriate graduations must be used for reconstitution to ensure accurate dosage.
The following steps should be followed for reconstitution:
1. Remove the coloured cap from the vial and wipe the top with an alcohol wipe.
2. Reblozyl 25 mg powder for solution for injection: Add 0.68 mL WFI into the vial by means of a syringe with appropriate graduations with a needle directing the flow onto the lyophilised powder. Allow to stand for one minute. Each 25 mg single-dose vial will deliver at least 0.5 mL of 50 mg/mL luspatercept.
Reblozyl 75 mg powder for solution for injection: Add 1.6 mL WFI into the vial by means of a syringe with appropriate graduations with a needle directing the flow onto the lyophilised powder. Allow to stand for one minute. Each 75 mg single-dose vial will deliver at least 1.5 mL of 50 mg/mL luspatercept.
3. Discard the needle and syringe used for reconstitution. Do not use them for subcutaneous injection.
4. Gently swirl the vial in a circular motion for 30 seconds. Stop swirling and let the vial sit in an upright position for 30 seconds.
5. Inspect the vial for undissolved powder in the solution. If undissolved powder is observed, repeat step 4 until the powder is completely dissolved.
6. Invert the vial and gently swirl in an inverted position for 30 seconds. Bring the vial back to the upright position and let it sit for 30 seconds.
7. Repeat step 6 seven more times to ensure complete reconstitution of material on the sides of the vial.
8. Visually inspect the reconstituted solution prior to administration. When properly mixed, Reblozyl reconstituted solution is a colourless to slightly yellow, clear to slightly opalescent solution which is free of visible foreign particulate matter. Do not use if undissolved product or foreign particulate matter is observed.
9. If the reconstituted solution is not used immediately, see section 6.3 for storage conditions.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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